title: Growth hormone secretion is correlated with neuromuscular innervation rather than motor neuron number in early-symptomatic male amyotrophic lateral sclerosis mice.
abstract: GH deficiency is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, therapy with GH and/or IGF-I has not shown benefit. To gain a better understanding of the role of GH secretion in ALS pathogenesis, we assessed endogenous GH secretion in wild-type and hSOD1(G93A) mice throughout the course of ALS disease. Male wild-type and hSOD1(G93A) mice were studied at the presymptomatic, onset, and end stages of disease. To assess the pathological features of disease, we measured motor neuron number and neuromuscular innervation. We report that GH secretion profile varies at different stages of disease progression in hSOD1(G93A) mice; compared with age-matched controls, GH secretion is unchanged prior to the onset of disease symptoms, elevated at the onset of disease symptoms, and reduced at the end stage of disease. In hSOD1(G93A) mice at the onset of disease, GH secretion is positively correlated with the percentage of neuromuscular innervation but not with motor neuron number. Moreover, this occurs in parallel with an elevation in the expression of muscle IGF-I relative to controls. Our data imply that increased GH secretion at symptom onset may be an endogenous endocrine response to increase the local production of muscle IGF-I to stimulate reinnervation of muscle, but that in the latter stages of disease this response no longer occurs.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St Lucia 4072, Australia. s.ngo@uq.edu.au; or Prof Chen Chen, School of Biomedical Sciences, University of Queensland, St Lucia 4072, Australia. E-mail: chen.chen@uq.edu.au.
authors.forename: F J
authors.initials: FJ
authors.lastname: Steyn
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: M J
authors.initials: MJ
authors.lastname: Fogarty
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: P A
authors.initials: PA
authors.lastname: McCombe
authors.forename: M C
authors.initials: MC
authors.lastname: Bellingham
authors.forename: S T
authors.initials: ST
authors.lastname: Ngo
authors.forename: C
authors.initials: C
authors.lastname: Chen
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1